Figure 3
Bifurcation of RhoA-GTP protein levels in response to an external signal regulating the GTP loading rate of RhoA.
The signal can either increase (activation) or decrease (inhibition) the GTP loading rate. The response to activation/inhibition is shown on the right/left side of the bifurcation respectively. The red solid lines indicate stable states and the blue dashed lines indicate unstable states. The bifurcation illustrates the possible coexistence (for some range of the signal) of four states: (i) the (1, 0) state with high RhoA-GTP and low Rac1-GTP, which corresponds to A phenotype; (ii) the (0+, 1), which corresponds to M phenotype; (iii) the (1, 1), which correspond to A/M phenotype; (iv) the (0, 0) state, which corresponds to E/M phenotype. The corresponding bifurcation of Rac1-GTP protein levels is shown in Supplementary Information Section 5. Co-existence of different phenotypes is associated with a multistable phase, highlighted by different background colors (see legend at the bottom). Starting from the (0+, 1) state (M phenotype, at bottom left part of the red curve), the system stays in the M phenotype when the inhibition signal is reduced; further switching the inhibition signal to an increasing activation signal leads the system to undergo a transition to the (1, 0) state (A phenotype, at top right part of the red curve). The transition is indicated by the dashed upward arrow at the boundary of the phase {A, M} and {A}. Similarly, increasing the inhibition signal can induce the transition from the (1, 0) state (A phenotype) back to the (0+, 1) state (M phenotype), as indicated by the downward arrow at the boundary of the phase {M} and {A, M}. Besides, cells may switch to the A/M or E/M phenotype due to noise in gene expression.
